02.10.2024

Why propofol doesn’t trigger malignant hyperthermia while volatile anesthetics do

The ryanodine receptor 1 (RyR1) is a critical calcium release channel in skeletal muscle cells, essential for muscle contraction. Malfunction or dysregulation of RyR1 can lead to severe muscle disorders, including malignant hyperthermia (MH) – a life-threatening reaction to certain volatile anesthetics, which presumably bind and bias RyR1 to an open state, causing uncontrolled calcium release, increased sarcomere tension, and heat production.

Interestingly, unlike volatile anesthetics, propofol, a widely used intravenous anesthetic, has long been known to be safe for patients susceptible to malignant hyperthermia. However, the molecular mechanisms behind this, particularly its effects on RyR1, have remained unclear.

In a recent study, researchers investigated how propofol interacts with RyR1 at the molecular level. They found that propofol binds directly to RyR1 and inhibits its opening, which may explain its non-triggering effect in MH-susceptible patients.

The team employed several methods, including [3H]ryanodine binding assays, molecular dynamics simulations, photoaffinity labeling, and calcium imaging, to demonstrate that propofol binds to and inhibits RyR1 at clinically relevant concentrations.

Planar lipid bilayer recordings (using the Orbit mini) showed that propofol reduces the open probability of RyR1 in a dose-dependent manner.

In conclusion, these findings suggest that propofol may actively mitigate the clinical manifestations of MH or other conditions arising from increased RyR1 activation.

Find the full article here: Propofol binds and inhibits skeletal muscle ryanodine receptor 1

Studying single channels in lipid bilayers? Learn more about parallel lipid bilayer recordings here: https://www.nanion.de/products/orbit-16-tc/